Introduction: Congenital myasthenic syndromes refer to a heterogenic group of neuromuscular transmission disorders. CMS-subtypes are diverse regarding exercise intolerance and muscular weakness, varying from mild symptoms to life-limiting forms with neonatal onset. Long-term follow-up studies on disease progression and treatment-response in pediatric patients are rare.Patients and Methods: We analyzed retrospective clinical and medication data in a cohort of 32 CMS-patients including the application of a standardized, not yet validated test to examine muscular strength and endurance in 21 patients at the (...) last follow-up. Findings obtained in our cohort were compared with long-term follow-up studies of CMS-cohorts from the literature by considering the underlying molecular mechanisms. Outcomes of CMS-ST were compared to results of normal clinical assessment.Results: Thirty-two pediatric patients with defects in eight different CMS-genes were followed by a median time of 12.8 years. Fifty-nine percentage of patients manifested with first symptoms as neonates, 35% as infants. While 53% of patients presented a reduced walking distance, 34% were wheelchair-bound. Even under adequate therapy with pyridostigmine and 3,4-diaminopyridine, CHAT-mutations led to the progression of muscular weakness partly in combination with persistent respiratory and bulbar symptoms. RAPSN, CHRND, and CHRNB1 patients with neonatal manifestation, early respiratory problems, and bulbar symptoms showed a good and maintained treatment response. CHAT and CHRNE patients required higher PS dosages, whereas RAPSN patients needed a lower mean dosage at the last follow-up. The benefits of short-term medication and long-term progression of symptoms were highly dependent on the specific genetic defect. CMS-ST was carried out in 17/21 patients, determined affected muscle groups including bulbar and ocular symptoms, some of which were not reported by the patients.Conclusions: Our findings and comparison with the literature- suggest a better treatment-response and less severe progression of symptoms present in patients suffering from mutations in CMS-genes directly associated with receptor deficiency, while patients with defects leading to synaptopathy and presynaptic defects tend to have worse outcomes. Assessment of affected muscular groups and clinical symptoms by CMS-ST may be a useful tool for optimal therapeutic management of the patients, especially for future clinical studies. (shrink)

Some criticism of Della Volpe to the Lukacsian esthetics is presented. According to the Italian philosopher, a materialistic philosophy of art could not be established upon the concept of intuition. The basic categories should be the category of "cognitive plenitude" and the category of "specific language". It is, thus, proposed that the Della volpian system be taken into consideration as the true starting point for the reflexions upon art, upon the relationships between the work and the society, (...) upon the degree of knowledge produced by the artistic universe.São apresentadas algumas críticas de Della Volpe à estética lukacsiana. Segundo o filósofo italiano, uma filosofia da arte materialista não poderia estar fundamentada no conceito de intuição. As categorias básicas seriam a de "plenitude cognoscitiva" e de "linguagens específicas". Assim, propõe-se que o sistema dellavolpiano seja levado em consideração, como verdadeiro ponto de partida para as reflexões sobre arte, sobre as relações entre a obra e a sociedade e sobre o grau de saber que o universo artístico produz. (shrink)